Chloride secretion by canine tracheal epithelium: I. Role of intracellular c AMP levels.

We measured the short-circuit current (Isc) across canine tracheal epithelium and the intracellular cAMP levels of the surface epithelial cells in the same tissues to assess the role of cAMP as a mediator of electrogenic Cl secretion. Secretogogues fall into three classes: (i) epinephrine, prostaglandin (PG) E1, and theophylline decrease both Isc and cellular cAMP levels; (ii) PGF2 alpha and calcium ionophore, A23187, increase Isc without affecting cell cAMP levels at the doses employed; and (iii) acetylcholine, histamine, and phenylephrine do not alter either Isc or cAMP levels. These findings indicate that: (i) increases in cAMP or Ca activity stimulate electrogenic Cl secretion by the columnar cells of the surface epithelium; (ii) cAMP mediates the effects of PGE1 and beta-adrenergic agonists; (iii) a strict correlation between cAMP levels and Cl secretion rate is not apparent from spontaneous variations in these parameters or from dose-response relations of Isc and cAMP to epinephrine concentration; and (iv) acetylcholine, histamine, and phenylephrine, agents that stimulate electrically-neutral NaCl secretion by submucosal glands, do not evoke cAMP-mediated responses by the surface epithelium. Addition of 10(-6) M indomethacin (or other prostaglandin synthesis inhibitors) to the mucosal solution decreases Isc and cellular cAMP levels and reduces the release of PGE2 into the bathing media by 80%. Indomethacin does not interfere with the subsequent secretory response to PGE1. This suggests that endogenous prostaglandin production underlies the spontaneous secretion of Cl across canine tracheal epithelium under basal conditions.